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GPR39  -  G protein-coupled receptor 39

Homo sapiens

Synonyms: G-protein coupled receptor 39
 
 
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Disease relevance of GPR39

 

High impact information on GPR39

  • Antibody feeding experiments demonstrated that the epitope-tagged ghrelin receptor was constitutively internalized but could be trapped at the cell surface by an inverse agonist, whereas GPR39 remained at the cell surface [2].
  • GPR39 displayed a clear but lower degree of constitutive activity through the inositol phosphate and cAMP response element pathways [2].
  • In contrast, GPR39 signaled with the highest constitutive activity in respect of activation of serum response element-dependent transcription, in part, possibly, through G(12/13) and Rho kinase [2].
  • Although Zn(2+) stimulated inositol phosphate turnover, cAMP production, arrestin mobilization, as well as cAMP response element-dependent and serum response element-dependent transcriptional activity in GPR39-expressing cells as opposed to mock-transfected cells, no reproducible effect was obtained with obestatin in the GPR39-expressing cells [3].
  • In contrast, the potency and efficacy of Zn(2+) in respect of activating signaling indicates that this metal ion could be a physiologically relevant agonist or modulator of GPR39 [3].
 

Biological context of GPR39

 

Anatomical context of GPR39

 

Associations of GPR39 with chemical compounds

  • We could activate GPR39 by high concentrations of Zn(2+), demonstrating cell surface expression of a functional receptor that could elicit a Ca(2+) response [6].
  • The mRNA expression levels of GPR39 were negatively correlated to fasting glucose concentrations (r = -0.581, P = 0.023), while exhibiting a positive correlation to adiponectin mRNA expression levels (r = 0.674, P = 0.006) [1].
  • In vivo experiments in rats demonstrated that GPR39 is up-regulated in adipose tissue during fasting and in response to streptozotocin treatment, although its expression is kept constant in the liver from the same animals [9].
 

Other interactions of GPR39

  • The ligand-binding and functional properties of GPR38 and GPR39 remain to be determined [4].
  • Results Obese T2DM patients exhibited significantly lower GPR39 expression levels compared to lean (P = 0.016) and obese normoglycaemic subjects (P = 0.008), while no differences between lean and obese normoglycaemic patients were observed [1].
 

Analytical, diagnostic and therapeutic context of GPR39

References

  1. The obestatin receptor (GPR39) is expressed in human adipose tissue and is down-regulated in obesity-associated type 2 diabetes mellitus. Catalán, V., Gómez-Ambrosi, J., Rotellar, F., Silva, C., Gil, M.J., Rodríguez, A., Cienfuegos, J.A., Salvador, J., Frühbeck, G. Clin. Endocrinol. (Oxf) (2007) [Pubmed]
  2. Common structural basis for constitutive activity of the ghrelin receptor family. Holst, B., Holliday, N.D., Bach, A., Elling, C.E., Cox, H.M., Schwartz, T.W. J. Biol. Chem. (2004) [Pubmed]
  3. GPR39 Signaling Is Stimulated by Zinc Ions But Not by Obestatin. Holst, B., Egerod, K.L., Schild, E., Vickers, S.P., Cheetham, S., Gerlach, L.O., Storjohann, L., Stidsen, C.E., Jones, R., Beck-Sickinger, A.G., Schwartz, T.W. Endocrinology (2007) [Pubmed]
  4. Cloning and characterization of two human G protein-coupled receptor genes (GPR38 and GPR39) related to the growth hormone secretagogue and neurotensin receptors. McKee, K.K., Tan, C.P., Palyha, O.C., Liu, J., Feighner, S.D., Hreniuk, D.L., Smith, R.G., Howard, A.D., Van der Ploeg, L.H. Genomics (1997) [Pubmed]
  5. Growth hormone releasing substances: types and their receptors. Smith, R.G., Palyha, O.C., Feighner, S.D., Tan, C.P., McKee, K.K., Hreniuk, D.L., Yang, L., Morriello, G., Nargund, R., Patchett, A.A., Howard, A.D. Horm. Res. (1999) [Pubmed]
  6. Obestatin does not activate orphan G protein-coupled receptor GPR39. Lauwers, E., Landuyt, B., Arckens, L., Schoofs, L., Luyten, W. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  7. Obestatin acts in brain to inhibit thirst. Samson, W.K., White, M.M., Price, C., Ferguson, A.V. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2007) [Pubmed]
  8. Relative gene-silencing efficiencies of small interfering RNAs targeting sense and antisense transcripts from the same genetic locus. Hu, X., Hipolito, S., Lynn, R., Abraham, V., Ramos, S., Wong-Staal, F. Nucleic Acids Res. (2004) [Pubmed]
  9. GPR39 splice variants versus antisense gene LYPD1: expression and regulation in gastrointestinal tract, endocrine pancreas, liver, and white adipose tissue. Egerod, K.L., Holst, B., Petersen, P.S., Hansen, J.B., Mulder, J., Hökfelt, T., Schwartz, T.W. Mol. Endocrinol. (2007) [Pubmed]
 
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